Vanderbilt University, Department of Radiology, 21st and Garland, Nashville, TN 37232-5316, Ph: 615-343-0595, Fax: 615-343-4890,

Regional Perinatal Center, Springfield MO 65807

Synonyms: Cryptodidymus, double monster, endocyme fetus, fetiform teratoma, fetal inclusion, included heteropagus twin, suppressed twin.

Definition: A fetus-in-fetu is an encapsulated, pedunculated vertebrate tumor. The minimal criteria generally required include the presence of an axial skeleton or a fetus with metameric organization, skin coverage, encapsulation and a two vessel cord (see text).

Prevalence: About 70 cases^{1-62, 64-65}, including six detected in utero^1-6, have been reported. An estimate of 0.02:10,000 is commonly reported, but this number is based on the unsubstantiated assumption that fetus-in-fetu represent 5% of conjoined twins⁷.

Etiology: Several etiologies have been proposed:

1)     a primordial organizer defect⁸,

2)     germ cells from the host that evolve on their own^3,9-12,

3)     a parthenogenetic origin,

4)     a continuum theory of evolution between monozygous twin to fetus-in-fetu¹³,

5)     an included monozygotic diamniotic parasitic twin¹⁴.

Pathogenesis: Retroperitoneal and testicular location: anastomosis between vitelline circulation of mono­zygotic diamniotic twins. Intracranial location: second differentiation foci of the bilaminar embryo, which is engulfed in the invagination of cells at Hensen"s node.

Associated anomalies: In the host: complications due to the space-occupying nature of the lesion and (one each): cutaneous angioma and Meckel diverticulum. For the fetus-in-fetu: essentially every anomaly resulting from hypoxic and arrested growth has been described. This is manifested by omphaloceles, major neural tube defects (an­en­ce­pha­ly and rachischisis), limb deficiencies and hypo- or aplasia of the organs derived from the meso- and endoderm.

Differential diagnosis: Teratoma.

Prognosis: Excellent for the host.

Recurrence risk: No recurrences have been reported.

Management: Surgical removal.

MESH Monsters-pathology, -etiology; Fetus-pathology; Teratoma-diagnosis; Diseases-in-Twins; ICD9 651.8 CDC 651.800

Introduction

The discovery of a fetus inside a child or a male adolescent is such a fascinating finding that records of these events have existed for many years^15-20. In the older literature, confusion existed between fetus-in-fetu and more common entities such as abdominocyesis and teratoma. However, well-documented cases in children and male adolescents have been reported. We report a case in which the findings were recognized in utero.

Case report

A 23-year-old, G₃P₂, white woman presented at 30 weeks gestation for evaluation of a fetal intra-abdominal cystic mass recognized at routine obstetrical sonography. Ultrasound revealed a single infant in oblique presentation. The amniotic fluid volume was normal. Normal fetal limb and cardiac activity were observed. The examination of the fetal anatomy was entirely normal with the exception of a lower abdominal mass (fig. 1, 2). This 52 x 37mm mass was separate from the bladder. The cystic mass contained a solid component within it, which was heterogeneous. The differential diagnosis included an anterior meningomyelocele, although the normal course of the aorta made that diagnosis very unlikely. The differential diagnosis also included a mesenteric cyst or an anterior sacrococcygeal teratoma. However, the working diagnosis was an ovarian cyst, since this was a female fetus.

30 weeks. Longitudinal and axial views of the abdominal mass which is located posteriorly.

The patient was followed over the next 10 weeks, and the cystic structure and the solid mass within it continued to enlarge. At 38 weeks, the cystic mass measured 77 x 55 mm, and about half of the internal volume of the cyst was occupied by the solid heterogeneous mass (fig. 3-5). Because this baby would require pediatric surgical services after birth, arrangements were made for delivery at a tertiary care center where a pediatric surgeon was available.

At 39 weeks, the patient underwent a primary cesarean section for fetal macrosomia and the presence of a large fetal abdominal cyst. A 4,300g female infant was delivered with Apgars of 8 and 9 at 1 and 5 minutes, respectively. A large mobile abdominal mass was palpable in the fetal abdomen immediately after delivery. At exploratory laparotomy, the mass proved to represent a fetus-in-fetu. Both the mother and the baby were discharged from the hospital following uneventful post-operative course.

Synonyms

As for any unusual anomalies, several descriptive terms have been used. These include:

• cryptodidymus kripto = hidden, didumoV = twin,
• dermocyma (derma = skin, kuma = fetus),
• double monster,
• endocyme fetus (endon = inside, kuma = fetus) [note that the word fetus is redundant],
• fetiform teratoma,
• fetal inclusion,
• included heteropagus twin (eteroV = other, pagoV = which is fixed) and
• suppressed twin.

Definition

A fetus-in-fetu is an encapsulated, pedunculated vertebrate tumor. It represents a malformed mono­zygotic, monochorionic diamniotic parasitic twin included in a host (or autosite) twin (see Etiology below). Characteristically the fetus-in-fetu complex will be composed of a fibrous membrane (equivalent to the chorioamnionic complex) that contains some fluid (equivalent to the amniotic fluid) and a fetus suspended by a cord or pedicle. The presence of a rudimentary spinal architecture is used to differentiate a fetus-in-fetu from a teratoma, since teratomas are not supposed to develop through the primitive streak stage (12-15 days). This last criterion has been considered too stringent by many authors who regard a rudimentary body architecture (metameric segmentation, craniocaudal and lateral differentiation, body coelom, "gestational sacâ€)^11,21, or the presence of an associated fetus-in-fetu^22,23 as equivalent criteria. Although teratomas can achieve striking degrees of differentiation by the inductive effect of adjacent tissues on one another^24-27, they do not present the criteria mentioned above.

P revalence

The prevalence is unknown. About 70 cases have been reported^{1-62, 64-65} but this number varies according to how strictly identification criteria are used (see Definition above). Several cases are formally recognized by some as fetus-in-fetu, while categorically rejected by others²². Seven cases (including the present case) have been detected in utero1-6. An estimated frequency of 0.02:10,000 is commonly reported in the literature⁷, but this number is based on the unsubstantiated assumption that fetus-in-fetu represents 5% of conjoined twins. Further, (see Etiology) the current trend is to consider that fetus-in-fetu does not represent a form of conjoined twins. The male-to-female ratio in the 39 reports that we reviewed was M1.3:F1. This is in contrast with conjoined twin, which occurs predominantly in girls.

Historical review

Several reports of fetus-in-fetu have appeared in the older literature. Until the first quarter of this century, no distinction existed between teratoma and fetus-in-fetu. Thus, reports that did not clearly identify the presence of a spine are subject to caution⁵². Further, because of possible confusion with abdominocyesis, cases in women of child-bearing age should be interpreted cautiously. The most credible old cases are those reported by Young¹⁵, Highmore¹⁶ and Taylor¹⁸. Only the first two reports include figures. Young reports the case of an 18-week-old boy examined for vomiting. On physical examination, a smooth, round tumor was palpated in the left upper quadrant. The patient was lost to follow-up but returned 5 months later, emaciated. The tumor had grown and extended to the scrobiculus cordis (the epigastric fossa), and the child poorly tolerated breast-feeding. Young describes episodes of enlargement and decrease of the abdominal perimeter, which he attributes to accumulation of fluid in the cyst. The child died at 9 months. On autopsy, a large mass occupying most of the abdomen was found. Opening the cyst revealed the fetus-in-fetus. Young gives a remarkably complete description of the findings.

Abdomen of the host.

right side

left side

Case of Young¹⁵.

The case reported by Highmore is even more extraordinary in that it occurred in a teenage boy. This 15-year-old boy had a 7-year history of abdominal complaints and mass. As in the previous case, the child died of malnutrition. At autopsy, a large tumor containing a fetus was discovered.

Etiology

Several etiologies have been proposed.

·        A primordial organizer defect was once thought to explain dermoids, teratoma and embryoma⁸.

·        Another theory suggested that the fetus-in-fetu derived from germ cells from the host that evolved on their own. This appears to be supported by the occasional localization in an ectopic testicle^9-12. However, that localization can also result from migration of the fetus-in-fetu along with the germ cells, when the germ cells of the host return from the yolk sac into the retro­peritoneal cavity on their way to the gonads.

·        A parthenogenetic origin has also been suspected. In this theory, germ cells from the retroperitoneal region (where they normally are located) are parthenogenetically stimulated and evolve into a rudimentary fetus. Histocompatibility studies and gene markers do not support parthenogenesis as a likely etiology⁴¹.

·        In the continuum theory of monozygous twin, a progression from normal twin to conjoined symmetrical twins into asymmetrical twin (acardiac twins) and then into parasitic twins, included twins and then teratoma is hypothesized¹³. As mentioned under Prevalence, the incidence is about equally divided among sexes (with a slight male predominance in this review), which is an argument against the continuum theory and the highly differentiated sacrococcygeal teratoma theory since conjoint twins and sacrococcygeal teratomas are more common in females.

Willis considered that the fetus-in-fetu did not represent a monoamniotic twin but instead an included monozygotic diamniotic parasitic twin within the host twin¹⁴: "It is, I believe, a mistake to suppose that a gentle series of gradations exists between double monsters and malformed twins on one hand and teratomas on the other—a mistake widely promulgated because of the prevalent view that teratomas are included monsters or malformed twins. The sooner this misconception is abandoned, the betterâ€⁶⁶. His postulate explains why in all extracranial locations the fetus-in-fetu is embedded in a gestational sac. If the fetus-in-fetu is a conjoined twin, it would have to be monoamniotic and thus would not have its own gestational sac. This theory has been widely accepted.

Pathogenesis

The accepted mechanism is the embedding of a twin due to vitelline circulation anastomoses. Vascular anastomoses between twins have variable repercussions, depending on the vessels anastomosed and the location of the anastomoses. The most benign anastomoses are superficial connections of similar vessels on the surface of the placenta. These connections between artery and artery or vein and vein are common and of limited significance when they occur after the first few weeks of gestation. When they occur early, and one fetus has a slight developmental delay, they result in the twin reversed arterial perfusion syndrome. Ana­stomoses that are between dissimilar vessels and occur in the placenta are responsible for the twin to twin transfusion syndrome.

Finally, anastomoses between vitelline vessels—only possible when the twins are monochorio­nic—are assumed to cause fetus-in-fetu by a mechanism similar to that which produces acar­diac twins. The cardiac development of the affected twin is impaired by the reversal of the flow in its heart. This stunts the growth of the affected fetus, and as the host grows it progressively embeds the smaller twin around the third week.

A few intracranial cases have been described^21,22,28. The location in the skull results from a different embryological mechanism. To be imbedded in the ventricle, a fetus-in-fetu has to separate at a much latter date than those that are imbedded in the retroperitoneum. At 15  days, when the embryo is at the bilaminar disc level, the primitive streak develops. At the cephalic end of the streak, a depression, the primitive knot or Hensen"s node, forms and extends cranially. The invagination of the cells into the depression is at the origin of the mesoderm and forms the notochordal process (or blastopore). The blastopore extends to become the notochord, which elongates towards the cranial end. If a second differentiation focus occurs in the bilaminar embryo and grows at the same rate as the primary focus, it will form a craniopagus conjoint twin. If the second differentiation focus grows slower than the primary focus, it will be engulfed in the invagination of cells and may arrest in what will ultimately become the ventricles. 

Although not reported, a fetus-in-fetu might thus also arrest along the central canal of the spinal cord. In intracranial fetus-in-fetu, one does not expect to find a gestational sac (amnion or chorion equivalent), and indeed none of the intracranial cases has described any surrounding membranes.

Localization

The majority of fetus-in-fetu are retroperitoneal²¹, but some have been found in the mesentery^50,57, adrenal⁴, cranial cavity²², lateral ventricles, pelvis⁵⁰, coccyx⁴⁶, inguinal region⁴⁷, testicles^9-12 and scrotum⁴⁵. 

Thus, most of the resting places are retroperitoneal or on the path that the germ cells follow on their way back from the yolk sac to the retroperitoneum and to the gonads. When located on ectopic testes, they may be intraperitoneal¹⁰. The affected testicle is usually ectopic or undescended, probably because the added bulk impairs the migration of the cells.

Vascularization

As expected from the etiology, most fetus-in-fetu are connected to the host by vessels originating from or around the superior mesenteric artery²¹; a derivative of the right vitelline artery in mammals. The artery of the fetus-in-fetu derives from the vitelline artery and thus is the equivalent of a superior mesenteric artery. In the host, if the superior mesenteric artery is not directly involved, the connection is usually with direct branches from the aorta, small retroperitoneal or diaphragmatic vessels (fig. 10). In a testicular location, spermatic vessels^4,9 or even renal and adrenal vessels may be involved. In only a few cases, a definite vascular connection can be recognized between the fetus-in-fetu and the host^7,50. In other cases, a capillary system exists between the two circulations. Since the fetus-in-fetu does not have a cardiac system, the severe hypoxia is responsible for the lack of evolution.

Age at detection

Only a few cases have been detected prenatally^1-6. Most cases are now discovered in newborns or small children. Figure 11 demonstrates the time at detection and the sometimes long delay before removal.

Weight

The weight varies from a few grams up to 2000⁵⁹ or even 4000g³⁸ (fig. 12). There is some inexactitude in the report of the weights since some reports mention the weight of the whole tumor, while others report the weight of the fetus-in-fetu alone.

Presenting symptoms in children

Aside from a few fortuitous discoveries, the disorder usually becomes apparent from its compression of adjacent organs, principally the gastrointestinal tract.

Number

Usually one fetus is found, but several instances of two^{5,,21,40,42-43,55} three⁵⁰, five22 or even more²³ have been described. When several fetuses are present, they usually share a same sac⁵⁰, but some have their own sacs⁴³.

Zygosity

Studies of gonads^52,73, blood types^7,31,50, chromosomes^7,41 and red cell antigens (ABO, Rh, M, N, S, P1, K, Fy and Jk)³¹ have shown the fetus-in-fetu to be monozygotic to the host. It is not surprising, however, that the fetus-in-fetu has the same blood type as the host, since it is perfused by the host. There have been no recorded cases of dizygosity. However, as in acardiac twins, the combination of a normal twin with a twin that has lost a gonosomic chromosome and thus appears as a 45,X0 could potentially be found.

Macroscopic appearance

At surgery, the fetus-in-fetu appears as a well-circumscribed mass bound by a fibrous membrane. Inside the mass the fetus-in-fetu is suspended in straw-colored fluid by a pedicle. Two vessels (an artery and a vein) travel along the pedicle. The fluid is generally not abundant and has been described as containing sebaceous material. The origin of this fluid is uncertain. Several authors have pointed out that the membranes of a normal embryo are not responsible for the production of amniotic fluid. They would more likely act as semipermeable membrane. In fetuses past 12 weeks, the urinary system produces the fluid and the gastrointestinal system resorbs it. Since no fetus-in-fetu has ever been described to contain a urinary system, and the segments of gastrointestinal tract that are found are too incomplete to have any reabsorptive capabilities, the fluid is probably maintained in the amniotic cavity solely by osmotic and oncotic pressure.

The presence of chorionic villi has only been reported in one case⁴⁹. Except for one quote of a 15-year old-saying "Mother, do come to me, I have something alive in my bodyâ€, and the mother being quoted as saying that she felt something resembling "the motion of a child during gestationâ€, no fetal movements have ever been recorded in a fetus-in-fetu. The above record of movement is somewhat doubtful since striated muscles have rarely been found around joints. Yet this host is one of the older hosts described (fig. 7).

What is included

Fetuses in fetu resemble poorly formed acardiac twins. Most every organ has been recognized in various stages of development. The notable exception is the urinary tract, which does not appear to have been recognized in any of the cases that we reviewed.

Some structures such as ribs⁷, intrathoracic organs (lung¹², heart, thymus⁵⁷) and retroperitoneal organs (liver, spleen, kidneys, adrenal glands³⁴, pancreas^34,57, gonads^11,34,52,73) are rarely described. An incomplete heart has been found^{7,22,57,61-62}. In one instance, a rudimentary 2-chamber heart was found with the atrium in the caudal position and the ventricle in the cranial position⁷. This is the stage normally reached in a 22-day embryo⁶⁷. Facial and cranial structures also are uncommonly seen, yet eyes³⁴, ears, mouth and poorly organized brain and cerebellum have been observed^{12,20,23,29,31,34, 50,57,65}.

The cord that connects the fetus to the membrane has different characteristics than a normal cord: it contains vasa vasorum and nerve fibers.

The evolution of the fetus-in-fetu is usually arrested at the first trimester, and further evolution is by mass accretion more than by development. Overall structures derived from the ectoderm are better represented than structures derived from the other two layers. The mesoderm contributes the musculoskeletal system which is usually well represented, but the other derivatives (the vascular and urogenital system, the spleen and adrenal glands) are uncommonly found. The most commonly represented derivative from the endodermal layer is the gastrointestinal tract, but the liver and pancreas are also often recognized.

Ultrasound appearance

The few cases detected prenatally all presented as a complex mass. The general appearance is a well-delineated capsule, with an echogenic mass suspended in fluid or partially surrounded by fluid. Occasionally, the diagnosis can be suggested by the recognition of a rudimentary spine, as in the present case.

Differential diagnosis

When discovered in a newborn child during physical examination, the differential diagnosis includes all the common masses such as Wilms" tumor, hydro­ne­phrosis, and neuroblastomas. Prenatally, the main differential diagnosis is with teratoma. Teratomas are disorganized congregations of pluripotential cells from all three primitive tissue layers. By differentiation and induction, they can achieve striking organization, with examples of several organs being well formed. However, teratomas do not have vertebral segmentation, craniocaudal and lateral differentiation, body coelom or systemic organogenesis. Thus the presence of a mass with a spinal organization and surrounded by fluid suggests the correct diagnosis.

When spinal structures are not present, most authors have considered that the diagnosis of fetus-in-fetu can still be made when the alternate criteria described under Definition are found56. These criteria are sufficiently restrictive that even well-organized teratomas cannot fulfill all of them.

Teratomas have a definite malignant potential, a feature that has not been reported in fetus-in-fetu. Teratomas occur predominantly in the lower abdomen, not the upper retroperitoneum. Yet, the coexistence of a fetus-in-fetu and a teratoma6,35,51 as well as the occurrence of a teratoma40 14 years after removal of a twin fetus-in-fetu42 have been reported, supporting the older hypothesis of a continuum between twin and teratoma. Cases of sacrococcygeal fetus-in-fetu should probably be regarded and treated as teratoma, because of the high incidence of teratoma in this region58,68.

Ectopic testicles have a higher incidence of germ cell tumors⁷², and the differentiation between fetus-in-fetu and teratoma is particularly important. Although the characteristics of intracranial teratoma differ from those of intracranial fetus-in-fetu, Wakai found, in a large review of 245 intracranial teratomas, that there are some transitions between certain teratoma and fetus-in-fetu⁶³.

In the older literature, several descriptions of fetus-in-fetu were too vague to be acceptable by current criteria. For example, the case reported by Phillips does not unequivocally suggest the criteria described above and therefore should probably be considered a teratoma¹⁷.

Some have argued that fetus-in-fetu should be considered as teratomas since they do not evolve into lithopedion like fetuses of abdominocyesis³. That argument is probably not valid since in abdominocyesis the antigen complements of the host and fetus are different, which contrasts with fetuses in fetu.

Associated anomalies

Every organ of the fetus-in-fetu has undergone hypoxic growth and is deformed. Most cases are anencephalic. Usually the body is closed, but ventral wall defects such as omphalocele are common, and a case that suggests a limb-body wall complex has also been described²². The host rarely presents any anomalies, except those related to the presence of a space-occupying lesion. Those manifestations have rarely been severe, even in the case of intracranial fetus-in-fetu²⁸, although in rare cases, severe hydrocephalus was responsible for the death of the host^{22, 23}. One case of Meckel diverticulum and another of skin hemangioma have been described. A malignant degeneration has never been reported, even in the cases that have been allowed to evolve for several years.

Evolution

Left alone, fetus-in-fetu do not seem harmful to the host, but in every case in which the fetus-in-fetu was not removed at the time of discovery, a slow growth has been described^21,38,44.

Prognosis

In the literature of the past century, fetus-in-fetu was fatal to the host because of the compression imposed to adjacent organs^15-17. In the more recent literature, the outcome for the host twin is usually favorable. Only a few cases of spontaneous12or postsurgical deaths are recorded^7,22,32,44.

Recurrence risk

There is no report of recurrence.

Management

Aside from a few attempts, in the first half of this century^36,73 to marsupialize fetus-in-fetu, surgical removal is the treatment of choice. The membranous capsule can usually be enucleated from the host with minimal problems. In only a few cases, removal is difficult due to adhesions^21,37,38, and this difficulty may precipitate the end of the operation^36,53 or even be the reason of the postoperative death of the host⁴⁴. Leaving the capsule, or part of it, has not led to complications, except in very rare cases in which fluid reaccumulated in it³⁶.

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